Nature aging最新文献

{"title":"Single-nucleus sequencing reveals enriched expression of genetic risk factors in extratelencephalic neurons sensitive to degeneration in ALS","authors":"Francesco Limone, Daniel A. Mordes, Alexander Couto, Brian J. Joseph, Jana M. Mitchell, Martine Therrien, Sulagna Dia Ghosh, Daniel Meyer, Yingying Zhang, Melissa Goldman, Laura Bortolin, Inma Cobos, Beth Stevens, Steven A. McCarroll, Irena Kadiu, Aaron Burberry, Olli Pietiläinen, Kevin Eggan","doi":"10.1038/s43587-024-00640-0","DOIUrl":"10.1038/s43587-024-00640-0","url":null,"abstract":"Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by a progressive loss of motor function linked to degenerating extratelencephalic neurons/Betz cells (ETNs). The reasons why these neurons are selectively affected remain unclear. Here, to understand the unique molecular properties that may sensitize ETNs to ALS, we performed RNA sequencing of 79,169 single nuclei from cortices of patients and controls. In both patients and unaffected individuals, we found significantly higher expression of ALS risk genes in THY1+ ETNs, regardless of diagnosis. In patients, this was accompanied by the induction of genes involved in protein homeostasis and stress responses that were significantly induced in a wide collection of ETNs. Examination of oligodendroglial and microglial nuclei revealed patient-specific downregulation of myelinating genes in oligodendrocytes and upregulation of an endolysosomal reactive state in microglia. Our findings suggest that selective vulnerability of extratelencephalic neurons is partly connected to their intrinsic molecular properties sensitizing them to genetics and mechanisms of degeneration. Using single-nucleus RNA sequencing data from patients with sporadic amyotrophic lateral sclerosis (ALS) cortices, the authors find that higher expression of ALS risk genes is accompanied by upregulation of stress responses in groups of extratelencephalic neurons. Analyses of glial nuclei revealed a downregulation of myelination genes in oligodendrocytes and upregulation of reactive state genes in microglia.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"4 7","pages":"984-997"},"PeriodicalIF":17.0,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s43587-024-00640-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141437976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Principal component-based clinical aging clocks identify signatures of healthy aging and targets for clinical intervention","authors":"Sheng Fong, Kamil Pabis, Djakim Latumalea, Nomuundari Dugersuren, Maximilian Unfried, Nicholas Tolwinski, Brian Kennedy, Jan Gruber","doi":"10.1038/s43587-024-00646-8","DOIUrl":"10.1038/s43587-024-00646-8","url":null,"abstract":"Clocks that measure biological age should predict all-cause mortality and give rise to actionable insights to promote healthy aging. Here we applied dimensionality reduction by principal component analysis to clinical data to generate a clinical aging clock (PCAge) identifying signatures (principal components) separating healthy and unhealthy aging trajectories. We found signatures of metabolic dysregulation, cardiac and renal dysfunction and inflammation that predict unsuccessful aging, and we demonstrate that these processes can be impacted using well-established drug interventions. Furthermore, we generated a streamlined aging clock (LinAge), based directly on PCAge, which maintains equivalent predictive power but relies on substantially fewer features. Finally, we demonstrate that our approach can be tailored to individual datasets, by re-training a custom clinical clock (CALinAge), for use in the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE) study of caloric restriction. Our analysis of CALERIE participants suggests that 2 years of mild caloric restriction significantly reduces biological age. Altogether, we demonstrate that this dimensionality reduction approach, through integrating different biological markers, can provide targets for preventative medicine and the promotion of healthy aging. Using a dimensionality reduction approach, Fong et al. generated a clinical aging clock (PCAge) that delineates healthy and unhealthy aging trajectories. They provide a streamlined version (LinAge) that maintains predictive power, and they demonstrate how the clock can be tailored to available data using the CALERIE study.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"4 8","pages":"1137-1152"},"PeriodicalIF":17.0,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s43587-024-00646-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141428550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Latin American brain-health research requires regional data and tailored models","authors":"","doi":"10.1038/s43587-024-00656-6","DOIUrl":"10.1038/s43587-024-00656-6","url":null,"abstract":"We reveal considerable heterogeneity in risk factors for healthy aging in Latin America, which underscores the limitations of existing, unharmonized research models for diverse populations. Our results emphasize the urgent need for region-specific studies that describe particular risks for Latin American aging to develop tailored preventive models and interventions.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"4 8","pages":"1041-1042"},"PeriodicalIF":17.0,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141422352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Social connection affects end-of-life well-being","authors":"Anna Kriebs","doi":"10.1038/s43587-024-00658-4","DOIUrl":"10.1038/s43587-024-00658-4","url":null,"abstract":"","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"4 6","pages":"751-751"},"PeriodicalIF":17.0,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141422354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Slowing early Parkinson’s disease","authors":"George Andrew S. Inglis","doi":"10.1038/s43587-024-00660-w","DOIUrl":"10.1038/s43587-024-00660-w","url":null,"abstract":"","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"4 6","pages":"748-748"},"PeriodicalIF":17.0,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141422353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Healthy aging meta-analyses and scoping review of risk factors across Latin America reveal large heterogeneity and weak predictive models","authors":"Agustin Ibanez, Marcelo Maito, Felipe Botero-Rodríguez, Sol Fittipaldi, Carlos Coronel, Joaquin Migeot, Andrea Lacroix, Brian Lawlor, Claudia Duran-Aniotz, Sandra Baez, Hernando Santamaria-Garcia","doi":"10.1038/s43587-024-00648-6","DOIUrl":"10.1038/s43587-024-00648-6","url":null,"abstract":"Models of healthy aging are typically based on the United States and Europe and may not apply to diverse and heterogeneous populations. In this study, our objectives were to conduct a meta-analysis to assess risk factors of cognition and functional ability across aging populations in Latin America and a scoping review focusing on methodological procedures. Our study design included randomized controlled trials and cohort, case–control and cross-sectional studies using multiple databases, including MEDLINE, the Virtual Health Library and Web of Science. From an initial pool of 455 studies, our meta-analysis included 38 final studies (28 assessing cognition and 10 assessing functional ability, n = 146,000 participants). Our results revealed significant but heterogeneous effects for cognition (odds ratio (OR) = 1.20, P = 0.03, confidence interval (CI) = (1.0127, 1.42); heterogeneity: I2 = 92.1%, CI = (89.8%, 94%)) and functional ability (OR = 1.20, P = 0.01, CI = (1.04, 1.39); I2 = 93.1%, CI = (89.3%, 95.5%)). Specific risk factors had limited effects, especially on functional ability, with moderate impacts for demographics and mental health and marginal effects for health status and social determinants of health. Methodological issues, such as outliers, inter-country differences and publication bias, influenced the results. Overall, we highlight the specific profile of risk factors associated with healthy aging in Latin America. The heterogeneity in results and methodological approaches in studying healthy aging call for greater harmonization and further regional research to understand healthy aging in Latin America. Ibanez et al. performed a scoping review and meta-analysis of healthy aging studies across Latin America and report substantial heterogeneity in how risk factors affect cognitive and functional ability, underscoring the need for further regional research.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"4 8","pages":"1153-1165"},"PeriodicalIF":17.0,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s43587-024-00648-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141422351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional declines raise risk of heatwave mortality","authors":"Hannah Walters","doi":"10.1038/s43587-024-00659-3","DOIUrl":"10.1038/s43587-024-00659-3","url":null,"abstract":"","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"4 6","pages":"749-749"},"PeriodicalIF":17.0,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141322263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Addressing gender disparities in global health","authors":"Yahyah Aman","doi":"10.1038/s43587-024-00661-9","DOIUrl":"10.1038/s43587-024-00661-9","url":null,"abstract":"","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"4 6","pages":"750-750"},"PeriodicalIF":17.0,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141322262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Conserved epigenetic hallmarks of T cell aging during immunity and malignancy","authors":"Tian Mi, Andrew G. Soerens, Shanta Alli, Tae Gun Kang, Anoop Babu Vasandan, Zhaoming Wang, Vaiva Vezys, Shunsuke Kimura, Ilaria Iacobucci, Stephen B. Baylin, Peter A. Jones, Christopher Hiner, April Mueller, Harris Goldstein, Charles G. Mullighan, Caitlin C. Zebley, David Masopust, Ben Youngblood","doi":"10.1038/s43587-024-00649-5","DOIUrl":"10.1038/s43587-024-00649-5","url":null,"abstract":"Chronological aging correlates with epigenetic modifications at specific loci, calibrated to species lifespan. Such ‘epigenetic clocks’ appear conserved among mammals, but whether they are cell autonomous and restricted by maximal organismal lifespan remains unknown. We used a multilifetime murine model of repeat vaccination and memory T cell transplantation to test whether epigenetic aging tracks with cellular replication and if such clocks continue ‘counting’ beyond species lifespan. Here we found that memory T cell epigenetic clocks tick independently of host age and continue through four lifetimes. Instead of recording chronological time, T cells recorded proliferative experience through modification of cell cycle regulatory genes. Applying this epigenetic profile across a range of human T cell contexts, we found that naive T cells appeared ‘young’ regardless of organism age, while in pediatric patients, T cell acute lymphoblastic leukemia appeared to have epigenetically aged for up to 200 years. Thus, T cell epigenetic clocks measure replicative history and can continue to accumulate well-beyond organismal lifespan. Using an iterative boost and transplantation model to generate multilifetime T cells, Mi et al. show that cellular epigenetic age can be uncoupled from organism age. While naive T cells appear epigenetically young, memory T cells and T-ALL leukemia can exhibit epigenetic ages exceeding the organismal lifespan.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"4 8","pages":"1053-1063"},"PeriodicalIF":17.0,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s43587-024-00649-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141312624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SGLT2 regulates immune-mediated senolysis","authors":"Guangran Guo, Corina Amor","doi":"10.1038/s43587-024-00651-x","DOIUrl":"10.1038/s43587-024-00651-x","url":null,"abstract":"Inhibitors of sodium glucose co-transporter 2 (SGLT2) have long been used in the treatment of diabetes and cardiovascular disease, owing to their modulation of glucose levels. Katsuumi and colleagues now show that, in addition to their glycemic effects, SGLT2 inhibitors modulate senescence immune surveillance by downregulating PD-L1 expression on senescent cells.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"4 7","pages":"909-910"},"PeriodicalIF":17.0,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141302341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}